To maintain their stability, injectable peptide preparations, e.g., those of growth hormone, are provided in two-component forms consisting of a dried pharmaceutical component prepared by lyophilization, for example, and a liquid pharmaceutical component (a solvent liquid such as a buffered solution) in which the former component is dissolved to give an injectable liquid. And, to allow patients' easy and reliable handling of them, two-compartment syringes (also called dual-chamber cylinder ampoules) are widely employed, e.g., for human growth hormone preparations, in which those two components are contained separately from each other in a single syringe (FIG. 1).
A two-compartment syringe, as shown in FIG. 1 in a side cross-sectional view, in which the leftward direction represents the actual upward direction, is partitioned in its interior with two slidable walls in a liquid tight fashion (slidable front wall 2 and slidable rear wall 3) to enclose a front space 4 and a rear space 5. In the front space 4, slightly forward of the slidable front wall 2, an elongated longitudinal groove 6 is defined in the inner wall of the two-compartment syringe, which groove has a length enough to stride the thickness of the slidable front wall 2 (therefore being a little longer than the thickness of the slidable front wall 2), so that a bypass through the groove 6 may be created when the whole body of the slideable front wall 2 is placed within the range of the groove 6. In the front space 4 is enclosed a dried pharmaceutical component 10 such as a lyophilized powder, and in the rear space 5 a solvent liquid 11 used to dissolve the dried pharmaceutical component. At the front end of the two-compartment syringe 1, a septum which can be pierced by a double-ended needle, is provided, and, in the figure, a double-ended needle 15 is secured there piercing the septum, and they are covered with a protecting cap 16.
Mixing of the dried pharmaceutical component 10 and the solvent liquid 11 within the two-compartment syringe and injection of them are performed as follows: while the syringe is held with its front end facing upward, with a double-ended needle 15 piercing the septum, the slidable rear wall 3 is pushed in, and by this the slidable front wall 2 is also pushed in. When rear end of the groove 6 is exposed at the rear edge of the slidable front wall 2, a bypass is formed through the groove 6 between the front space 4 and the rear space 5, through which bypass the solvent liquid 11 contained in the rear space 5 begins to be transferred into the front space 4, whereas the slidable front wall 2 comes to a halt there. At the time when the slidable rear wall 3 comes to abut on the slidable front wall 2, all the solvent liquid 11 in the rear space 5 has been transferred into the front space 4 and mixes there with the pharmaceutical component 10 and dissolves it to form an injectable liquid. After this, as the slidable rear wall 3 and the slidable front wall 2 are pushed in a body, the device is handled in the similar manner to conventional one-compartment syringes.
In the case of a peptide hormone preparation, e.g., a growth hormone preparation, a long-term, regular and portionwise repeated administration is needed. Such administration is conducted at home by a patient himself or some other member of the patient's family (hereinafter referred collectively to as “patients”). The patients receive several two-compartment syringes containing undissolved pharmaceutical components together with an injection device into which one of such syringes is to be loaded, and they by themselves perform the processes of mixing of the pharmaceutical components to dissolve within the two-compartment syringe.
The present inventors found that, in the process of mixing the pharmaceutical agents in a two-compartment syringe, which is performed by patients at home, there are some cases in which the slidable rear wall is forcefully and abruptly pushed in, and the necessary cooperation of the front and rear slidable walls 2 and 3 thereby falls short, causing backward leak of the solvent liquid. Thus, there are needs for a device which would guarantee proper mixing of the pharmaceutical agents in a two-compartment syringe, as well as such a device which, in addition, would allow multiple repeated injections of a predetermined volume to be performed properly and easily after mixing. Further, in order to reduce their production cost, it is preferred that such a device could achieve the purpose without relying on a complex structure.
There are known some injection devices which are designed to be used to mix pharmaceutical agents in a two-compartment syringe and perform multiple portionwise injections. However, devices that allow patients to abruptly press in the slidable rear wall in the process of mixing/dissolving of the pharmaceutical agents (see Patent Documents 1 and 2) are not free of the risk of causing the above-mentioned problem of liquid leak. Though such devices are known that are designed so that the piston rod is slowly advanced by rotating a screw and the slidable rear wall is thereby slowly pressed in (see Patent Documents 4 and 5), it is quite troublesome for patients who daily handle such devices that they must rotate the screw with their hand in order to press in the piston rod.
An injection device is known which is provided with a spring to slowly advance the slidable rear wall of a two-compartment syringe (see Patent Document 6). With this device, when the front half of the body of the device holding a two-compartment syringe is inserted deep into the rear half of the body, a lock is released and a cylindrical plunger, being pressed from behind by a spring, is then advanced, which then make the slidable rear wall forwardly advance to mix the contained pharmaceutical agents. After mixing is completed, one of a small number of steps provided in helical arrangement on an injector rod inserted in the rear part of the plunger is positioned on a rib provided in the inside of the plunger and driven to push the latter, and a predetermined amount of the injectable liquid is thereby discharged through the needle. Though this device successfully eliminates the risk of being handled abruptly in mixing of the pharmaceutical agents contained in a two-compartment syringe, it is of a complex structure and consists of a number of components, and, further, it is difficult with this type of device either to provide such steps for adjustment precisely and at short intervals or to make it adapted to repeated multiple portionwise injections, since in the device, control of injection volume is done by engagement of steps provided in a helical arrangement around the thin injector rod with the rib provided in the inside of the plunger. Furthermore, after injection is done with this device, the spring, which is unlocked and extended, and the plunger, which now rests at its foremost position, would not return to their initial positions simply by removing the empty two-compartment syringe or pulling back the injector rod. Therefore, with this injection device, if no improvement is made, it is not easy to restore the initial condition of the device (where the spring is locked), and so the device at least is inconvenient for patients who repeatedly handle it by themselves.    [PATENT DOCUMENT 1] U.S. Pat. No. 4,874,381    [PATENT DOCUMENT 2] U.S. Pat. No. 6,053,893    [PATENT DOCUMENT 3] U.S. Pat. No. 6,419,656    [PATENT DOCUMENT 4] U.S. Pat. No. 4,968,299    [PATENT DOCUMENT 5] U.S. Pat. No. 5,080,649    [PATENT DOCUMENT 6] U.S. Pat. No. 6,793,646